Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract driven by an exaggerated immune response to luminal microbiota in susceptible individuals. It presents with a heterogenous pattern of clinical disease severity, location, and behavior. Understanding the interaction between the host genome, gut microbiome, and further environmental exposures in the development of IBD is in the early stages, and factors that trigger onset of disease in susceptible individuals remain unknown. This article addresses the genetic, microbial, and environmental influences on development of inflammatory bowel disease and the ability to manipulate these factors through surgery and medical therapy.